Estrogen receptor α gene analysis in girls with central precocious puberty.

OBJECTIVE: Estrogen is the final key factor that triggers the onset of puberty. The raised sensitivity of estrogen receptor, which may be caused by an estrogen receptor α (ERα) gene mutation or polymorphism, has been implicated in the etiology of precocious puberty. The aim of this study is to identify ERα gene mutations or polymorphisms in girls with central precocious puberty (CPP). METHODS: A total of 204 Korean girls with CPP were included in this study along with 102 healthy Korean female adults as controls. All coding exons and exon-intron boundaries of the ERα gene were sequenced. The relationship between identified sequence variations and CPP were evaluated via comparison of allele frequencies between the two groups. RESULTS: Eight polymorphisms were identified in the ERα gene. Among the eight polymorphisms in this study, five have been previously reported, whereas the other three were novel polymorphisms. Two of the three novel polymorphisms, p.G145S in exon 1 and p.R555H in exon 8 were only identified in the patient group. The subgroup with p.G145S showed a significantly higher level of peak luteinizing hormone than the subgroup without p.G145S in girls with CPP. CONCLUSION: The scanning and typing of ERα polymorphism has uncovered several potentially meaningful polymorphisms. However, no solid conclusion can be made from this study and further studies are necessary to validate the function of these polymorphisms.

Impact of body mass index on luteinizing hormone secretion in gonadotropin-releasing hormone stimulation tests of boys experiencing precocious puberty.

OBJECTIVE: Excess adiposity may influence various aspects of pubertal development, including the timing of pubertal initiation and hormonal parameters during puberty. The aim of the study was to evaluate the impact of body mass index (BMI) on luteinizing hormone (LH) secretion to gonadotropin-releasing hormone (GnRH) stimulation test in boys with precocious puberty. METHODS: Boys with precocious puberty, who were normal weight, overweight, and obese underwent GnRH stimulation tests between 2003 and 2010. Subjects were classified as normal weight (BMI ≥5th percentile and BMI <85th percentile), overweight (BMI ≥85th percentile and BMI <95th percentile), and obese (BMI ≥95th percentile). RESULTS: Of 56 children whose data were included in the final analysis, mean age at diagnosis was 8.7 ± 1.0 years. The majority of boys were of normal weight (n = 28, 50%), while 15 children (26%) were overweight, and 13 (23%) obese. Peak LH levels after GnRH stimulation were 19.8 ± 8.8, 9.0 ± 3.5, and 8.1 ± 4.0 mIU/ml among normal weight, overweight, and obese subjects, respectively (p < 0.001 for all comparisons). By multivariate analysis, there was a significant negative association of BMI with peak-stimulated LH level. CONCLUSIONS: The higher BMI is associated with lower LH response to the GnRH stimulation test in boys experiencing precocious puberty. In boys with precocious puberty, BMI should be considered when interpreting GnRH stimulation test.

Response to three years of growth hormone therapy in girls with Turner syndrome.

PURPOSE: Short stature is the most common finding in patients with Turner syndrome. Improving the final adult height in these patients is a challenge both for the patients and physicians. We investigated the clinical response of patients to growth hormone treatment for height improvement over the period of three years. METHODS: Review of medical records from 27 patients with Turner syndrome treated with recombinant human growth hormone for more than 3 years was done. Differences in the changes of height standard deviation scores according to karyotype were measured and factors influencing the height changes were analyzed. RESULTS: The response to recombinant human growth hormone was an increase in the height of the subjects to a mean value of 1.1 standard deviation for subjects with Turner syndrome at the end of the 3-year treatment. The height increment in the first year was highest. The height standard deviation score in the third year was negatively correlated with the age at the beginning of the recombinant human growth hormone treatment. Different karyotypes in subjects did not seem to affect the height changes. CONCLUSION: Early growth hormone administration in subjects with Turner syndrome is helpful to improve height response to the treatment.

Changes in bone mineral density and body composition in children with central precocious puberty and early puberty before and after one year of treatment with GnRH agonist.

BACKGROUND/AIMS: Much concern has been raised and debated on the effects of obesity and bone mineral density (BMD) after treatment with GnRH agonist. The aim of this study was to assess BMD and body composition, especially percent body fat (%FM) based on dual-energy X-ray absorptiometry (DEXA), before and after 1 year of treatment with GnRH agonist in Korean girls. METHODS: We assessed BMD and body composition in 121 Korean girls with precocious puberty before and after 1 year of treatment with GnRH agonist. BMD and body composition values were measured by using DEXA. RESULTS: The BMD standard deviation score of each region of interest for chronological age (CA) were higher than zero, but lower than zero for bone age (BA) at baseline and the gap was decreased after 1 year of GnRH agonist treatment. The fat mass (FM) and %FM for both CA and BA were significantly higher than zero at baseline. After GnRH agonist treatment, FM and %FM decreased for CA, but increased for BA. CONCLUSION: Pituitary-gonadal axis suppression by GnRH agonist does not reverse the progression of bone mass acquisition and does not increase the prevalence of obesity in Korean children with precocious puberty.

Virilizing adrenocortical carcinoma in a child with Turner syndrome and somatic TP53 gene mutation.

Virilizing adrenocortical carcinoma and Turner syndrome have opposite clinical manifestations in some aspects. Here, we report on the first case of virilizing adrenocortical carcinoma in a girl with Turner syndrome. A 2 10/12-year-old girl presented pubic hair of Tanner stage III with clitomegaly, deepening of her voice, and tall stature. No other morphologic anomaly was found. Biochemical assessment revealed normal electrolytes with pronounced elevation of adrenal androgens. She was found to have a large mass of the left adrenal gland on abdominal computed tomography scan. She underwent complete resection of the mass, and pathology was consistent with adrenocortical carcinoma. She was tested for TP53 gene mutation, and we found a de novo TP53 gene mutation (Val143Ala) as well as a 45,X karyotype.

Attenuated renal excretion in response to thiazide diuretics in Gitelman's syndrome: a case report.

Gitelman's syndrome is a variant of Bartter's syndrome characterized by hypocalciuria and hypomagnesemia. The administration of thiazide diuretics may induce a subnormal increase of urinary Na+ and Cl- excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less Na+ and Cl- than normal is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Specific mutations of NaCl cotransporter, coupled with mutant NaCl cotransporter expression studies clearly demonstrated that many of the characteristics of individuals with Gitelman's syndrome are explained by lack of function of NaCl cotransporter. We recently diagnosed a patient with Gitelman's syndrome by performing the thiazide and furosemide tests, and it is suggested that the clearance studies by diuretic administration may be of diagnostic help in Gitelman's syndrome.